This invention relates to ophthalmic preparations and methods of applying the preparations to the ocular surface. More particularly, it relates to ophthalmic preparations that permit essentially normal maintenance of ocular surface mucus-containing goblet cells.
The conjunctival epithelium of the eye contains mucus-containing goblet cells. These cells secrete mucus in a controlled fashion. They thereby form a major element of the biological system by which the surface of the eye protects itself from harmful foreign matter, including but not limited to infectious agents. The goblet cells also form a critical layer of the tear film of the eye that protects the surface of the eye from dessication. Furthermore, the mucus contained within these goblet cells is a major natural lubricant for the ocular surface. The presence of a normal density of goblet cells is important for the maintenance of a healthy ocular surface.
Medicamentosa is a disease of the surface of the eye caused by the frequent administration to the eye of topical medications and/or solutions. The disease can cause ocular irritation, photophobia, conjunctival injection and keratitis. The cause of this disease has been unclear. It now has been found, however, that exposing the surface of the eye to standard ophthlamic solutions results in an accelerated loss of mucus from the conjunctival goblet cells. This loss of mucus leaves the ocular surface with an abnormally low density of mucus-containing goblet cells. This abnormal loss of goblet cell mucus is a manifestation of toxicity of the solution that was used.
It is now postulated that one mechanism responsible for the development of medicamentosa is the gradual, progressive depletion of goblet cell mucus that the exposure to standard ophthlamic solutions induces. Derangement of goblet cell mucus can decrease the eye's ability to rid itself of harmful foreign material, can engender dessication of the ocular surface, and can decrease lubrication of the surface. For example, solutions designed to lubricate the eye in fact work against that intention when they deplete the eye of goblet cell mucus which is a most important natural lubricant.
It is desirable to minimize the toxicity of ophthalmic preparations. What is needed is an essentially non-toxic ophthalmic preparation which satisfies the fluid and electrolyte requirements of the ocular surface.
The composition of tear fluid has been determined to include proteins, enzymes, lipids, metabolites and electrolytes. The proteins include tear albumin, lysozyme, lactoferrin, transferrin, caeruloplasmin, immunoglobulins, complement, glycoproteins and antiproteinases. The enzymes include glycolytic enzymes and enzymes of the tricarboxylic acid cycle, as well as lactate dehydrogenase, lysosomal enzymes, amylase, peroxidase, plasminogen activator and collagenase. The lipids include cholestrol, though lipids from other lipid classes are present. The metabolites include glucose, lactate, urea, catecholamines, histamine, and prostaglandins. The electrolytes include sodium, potassium, calcium, magnesium, chloride and bicarbonate.
It is an object of this invention to provide an ophthalmic preparation which permits essentially normal maintenance of ocular surface mucus-containing goblet cells. Another object is to provide an ophthalmic preparation which is essentially non-toxic. Another object is to provide a preparation for the improved treatment of the spectrum of dry eye disorders. Another object is to provide a preparation for selectively increasing or decreasing tear film osmolarity. Still another object is to provide a preparation of the above character which is suitable selectively for contact lens adaptation, for use as a vehicle for medicaments, and for eye comfort in general. Another object is to provide an ophthalmic preparation which may serve as an irrigation fluid and/or drug vehicle in patients with extensive lacrimal gland and/or excretory duct destruction and/or other ocular diseases where continuous or nearly-continuous ocular irrigation and/or drug therapy is desirable.
Other objects of the invention will in part be obvious and will in part appear hereinafter.